No Impairment in Host Defense against Streptococcus pneumoniae in Obese CPEfat/fat Mice

Abstract

In the US and globally, dramatic increases in the prevalence of adult and childhood obesity have been reported during the last 30 years. In addition to cardiovascular disease, type II diabetes, and liver disease, obesity has recently been recognized as an important risk factor for influenza pneumonia. During the influenza pandemic of 2009, obese individuals experienced a greater severity of illness from the H1N1 virus. In addition, obese mice have also been shown to exhibit increased lethality and aberrant pulmonary inflammatory responses following influenza infection. In contrast to influenza, the impact of obesity on bacterial pneumonia in human patients is controversial. In this report, we compared the responses of lean WT and obese CPEfat/fat mice following an intratracheal infection with Streptococcus pneumoniae, the leading cause of community-acquired pneumonia. At 16 weeks of age, CPEfat/fat mice develop severe obesity, hyperglycemia, elevated serum triglycerides and leptin, and increased blood neutrophil counts. There were no differences between lean WT and obese CPEfat/fat mice in survival or lung and spleen bacterial burdens following intratracheal infection with S. pneumoniae. Besides a modest increase in TNF-α levels and increased peripheral blood neutrophil counts in CPEfat/fat mice, there were not differences in lung or serum cytokines after infection. These results suggest that obesity, accompanied by hyperglycemia and modestly elevated triglycerides, at least in the case of CPEfat/fat mice, does not impair innate immunity against pneumococcal pneumonia.

Diet‐induced obese mice exhibit altered immune responses to acute lung injury induced by Escherichia coli

“…We and others have observed that obese mice appear to exhibit significant alterations in leukocyte migration to the lungs after infection, particularly neutrophils .These abnormalities may be attributed to obesity‐induced impairments in pulmonary vascular homeostasis and enhanced susceptibility to acute injury . Neutrophils are known to ingest and kill bacteria, and elevated levels of PMNs may facilitate enhancements in host defenses against bacterial infections, contributing to host recovery.…”

A Comparative Study of Lung Host Defense in Murine Obesity Models. Insights into Neutrophil Function

“…Mancuso and colleagues (11,18) showed that obese, leptindeficient (ob/ob) mice exhibit increased susceptibility to infections with both gram-negative (K. pneumoniae) and gram-positive (Streptococcus pneumoniae) organisms, at 24 and 48 hours after inoculation, respectively, and that restoration of leptin levels could reverse the observed defects in bacterial clearance and survival (18). However, pulmonary host defense in hyperphagic CPE fat/fat mice (which manifest more modest metabolic abnormalities [25]) appeared to be normal at both 24 and 48 hours after infection with S. pneumoniae (19). Here, we report evidence of impaired pulmonary host defense in response to K. pneumoniae in both ob/ob and CPE fat/fat , as well as db/db and DIO, models of obesity, but with temporal variation.…”

“…Several animal models of obesity have been used to investigate the effects of obesity and associated comorbidities on the pulmonary immune response related to both acute and chronic lung diseases, including bacterial (11,12,18,19,27,29) and viral (9,28,39,40) respiratory infections, airway hyperresponsiveness (8,(41)(42)(43)(44)(45)(46), ARDS (5,7,12,30), pulmonary fibrosis (26), and chronic obstructive pulmonary disease (31). The most commonly employed mouse models of obesity include DIO, the hyperphagic mutant db/db, CPE fat/fat , and ob/ob strains.…”

“…Similar to these human studies, variable results were also found using mouse models of obesity. Susceptibility to and outcome of bacterial respiratory infection was increased in obese ob/ob mice compared with their lean controls (11,18), whereas no differences were observed between obese CPE fat/fat mice and their lean controls (19). Reasons for this inconsistency may include pathogen-specific defects in the immune response or differences in the metabolic state (lipid, glucose, and adipokine levels, among others) of individual subjects with obesity.…”

Integrative Physiology of Pneumonia

“…High circulating leptin content in mice, elevated by diverse strategies, can compromise innate immunity in the lungs (502). A specific role for leptin is further supported by the observation of no adverse effects on lung defense in a leptin-independent mouse model of obesity (307). The precise role of leptin is complicated by indirect metabolic consequences of its manipulation and the widespread physiological impacts of obesity (479).…”